Augmented Lagrangian method with nonmonotone penalty parameters for constrained optimization

At each outer iteration of standard Augmented Lagrangian methods one tries to solve a box-constrained optimization problem with some prescribed tolerance. In the continuous world, using exact arithmetic, this subproblem is always solvable. Therefore, the possibility of finishing the subproblem resolution without satisfying the theoretical stopping conditions is not contemplated in usual convergence theories. However, in practice, one might not be able to solve the subproblem up to the required precision. This may be due to different reasons. One of them is that the presence of an excessively large penalty parameter could impair the performance of the box-constraint optimization solver. In this paper a practical strategy for decreasing the penalty parameter in situations like the one mentioned above is proposed. More generally, the different decisions that may be taken when, in practice, one is not able to solve the Augmented Lagrangian subproblem will be discussed. As a result, an improved Augmented Lagrangian method is presented, which takes into account numerical difficulties in a satisfactory way, preserving suitable convergence theory. Numerical experiments are presented involving all the CUTEr collection test problems.

STATISTICAL TEST FOR GENOTYPE AND ENVIRONMENT CONTRIBUTION IN THE GENOTYPES x ENVIRONMENTS INTERACTION MATRIX

The objective of the present work was to propose a method for testing the contribution of each level of the factors in a genotypes x environments (GxE) interaction using multi-environment trials analyses by means of an F test. The study evaluated a data set, with twenty genotypes and thirty-four environments, in a block design with four replications. The sum of squares within rows (genotypes) and columns (environments) of the GxE matrix was simulated, generating 10000 experiments to verify the empirical distribution. Results indicate a noncentral chi-square distribution for rows and columns of the GxE interaction matrix, which was also verified by the Kolmogorov-Smirnov test and Q-Q plot. Application of the F test identified the genotypes and environments that contributed the most to the GxE interaction. In this way, geneticists can select good genotypes in their studies.

A rationale for long-lived quarks and leptons at the LHC: low energy flavour theory

In the framework of gauged flavour symmetries, new fermions in parity symmetric representations of the standard model are generically needed for the compensation of mixed anomalies. The key point is that their masses are also protected by flavour symmetries and some of them are expected to lie way below the flavour symmetry breaking scale(s), which has to occur many orders of magnitude above the electroweak scale to be compatible with the available data from flavour changing neutral currents and CP violation experiments. We argue that, actually, some of these fermions would plausibly get masses within the LHC range. If they are taken to be heavy quarks and leptons, in (bi)-fundamental representations of the standard model symmetries, their mixings with the light ones are strongly constrained to be very small by electroweak precision data. The alternative chosen here is to exactly forbid such mixings by breaking of flavour symmetries into an exact discrete symmetry, the so-called proton-hexality, primarily suggested to avoid proton decay. As a consequence of the large value needed for the flavour breaking scale, those heavy particles are long-lived and rather appropriate for the current and future searches at the LHC for quasi-stable hadrons and leptons. In fact, the LHC experiments have already started to look for them.

Milky Way demographics with the VVV survey I. The 84-million star colour-magnitude diagram of the Galactic bulge

Context. The Milky Way (MW) bulge is a fundamental Galactic component for understanding the formation and evolution of galaxies, in particular our own. The ESO Public Survey VISTA Variables in the Via Lactea is a deep near-IR survey mapping the Galactic bulge and southern plane. Particularly for the bulge area, VVV is covering similar to 315 deg(2). Data taken during 2010 and 2011 covered the entire bulge area in the JHKs bands. Aims. We used VVV data for the whole bulge area as a single and homogeneous data set to build for the first time a single colour-magnitude diagram (CMD) for the entire Galactic bulge. Methods. Photometric data in the JHK(s) bands were combined to produce a single and huge data set containing 173 150 467 sources in the three bands, for the similar to 315 deg(2) covered by VVV in the bulge. Selecting only the data points flagged as stellar, the total number of sources is 84 095 284. Results. We built the largest colour-magnitude diagrams published up to date, containing 173.1+ million sources for all data points, and more than 84.0 million sources accounting for the stellar sources only. The CMD has a complex shape, mostly owing to the complexity of the stellar population and the effects of extinction and reddening towards the Galactic centre. The red clump (RC) giants are seen double in magnitude at b similar to -8 degrees-10 degrees, while in the inner part (b similar to -3 degrees) they appear to be spreading in colour, or even splitting into a secondary peak. Stellar population models show the predominance of main-sequence and giant stars. The analysis of the outermost bulge area reveals a well-defined sequence of late K and M dwarfs, seen at (J - K-s) similar to 0.7-0.9 mag and K-s greater than or similar to 14 mag. Conclusions. The interpretation of the CMD yields important information about the MW bulge, showing the fingerprint of its structure and content. We report a well-defined red dwarf sequence in the outermost bulge, which is important for the planetary transit searches of VVV. The double RC in magnitude seen in the outer bulge is the signature of the X-shaped MW bulge, while the spreading of the RC in colour, and even its splitting into a secondary peak, are caused by reddening effects. The region around the Galactic centre is harder to interpret because it is strongly affected by reddening and extinction.

Recoupled separated-local-field experiments and applications to study intermediate-regime molecular motions

A specific separated-local-field NMR experiment, dubbed Dipolar-Chemical-Shift Correlation (DIPSHIFT) is frequently used to study molecular motions by probing reorientations through the changes in XH dipolar coupling and T-2. In systems where the coupling is weak or the reorientation angle is small, a recoupled variant of the DIPSHIFT experiment is applied, where the effective dipolar coupling is amplified by a REDOR-like pi-pulse train. However, a previously described constant-time variant of this experiment is not sensitive to the motion-induced T-2 effect, which precludes the observation of motions over a large range of rates ranging from hundreds of Hz to around a MHz. We present a DIPSHIFT implementation which amplifies the dipolar couplings and is still sensitive to T-2 effects. Spin dynamics simulations, analytical calculations and experiments demonstrate the sensitivity of the technique to molecular motions, and suggest the best experimental conditions to avoid imperfections. Furthermore, an in-depth theoretical analysis of the interplay of REDOR-like recoupling and proton decoupling based on Average-Hamiltonian Theory was performed, which allowed explaining the origin of many artifacts found in literature data. (C) 2012 Elsevier Inc. All rights reserved.

Real-time PCR quantitation of glucocorticoid receptor alpha isoform

Abstract Background The expression of glucocorticoid-receptor (GR) seems to be a key mechanism in the regulation of glucocorticoid (GC) sensitivity and is potentially involved in cases of GC resistance or hypersensitivity. The aim of this study is to describe a method for quantitation of GR alpha isoform (GRα) expression using real-time PCR (qrt-PCR) with analytical capabilities to monitor patients, offering standard-curve reproducibility as well as intra- and inter-assay precision. Results Standard-curves were constructed by employing standardized Jurkat cell culture procedures, both for GRα and BCR (breakpoint cluster region), as a normalizing gene. We evaluated standard-curves using five different sets of cell culture passages, RNA extraction, reverse transcription, and qrt-PCR quantification. Intra-assay precision was evaluated using 12 replicates of each gene, for 2 patients, in a single experiment. Inter-assay precision was evaluated on 8 experiments, using duplicate tests of each gene for two patients. Standard-curves were reproducible, with CV (coefficient of variation) of less than 11%, and Pearson correlation coefficients above 0,990 for most comparisons. Intra-assay and inter-assay were 2% and 7%, respectively. Conclusion This is the first method for quantitation of GRα expression with technical characteristics that permit patient monitoring, in a fast, simple and robust way.

Protein secretion in Lactococcus lactis : an efficient way to increase the overall heterologous protein production

Anderson MIYOSHI, Daniela FREITAS, Luciana RIBEIRO, Jane E. GABRIEL, Sophie LECLERCQ, Maricê N. OLIVEIRA, and Valeria D. GUIMARÃES were recipients of a CAPES fellowship (project CAPESCOFECUB #319II). Luis BERMUDEZ and Sébastien NOUAILLE were recipients of a fellowship from the French Ministry of Education and Research. INRA and Région IledeFrance also financed L. BERMUDEZ and V. GUIMARAES. Cathy CHARLIER is recipient of a fellowship from INRA and Région Bretagne.

Global gene expression profiling of oral cavity cancers suggests molecular heterogeneity within anatomic subsites

Abstract Background Oral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis. Results Samples of primary OSCCs and their corresponding surgical margins were obtained from male patients during surgery and their gene expression profiles were screened using whole-genome microarray technology. Hierarchical clustering and Principal Components Analysis were used for data visualization and One-way Analysis of Variance was used to identify differentially expressed genes. Samples clustered mostly according to disease subsite, suggesting molecular heterogeneity within tumor stages. In order to corroborate our results, two publicly available datasets of microarray experiments were assessed. We found significant molecular differences between OSCC anatomic subsites concerning groups of genes presently or potentially important for drug development, including mRNA processing, cytoskeleton organization and biogenesis, metabolic process, cell cycle and apoptosis. Conclusion Our results corroborate literature data on molecular heterogeneity of OSCCs. Differences between disease subsites and among samples belonging to the same TNM class highlight the importance of gene expression-based classification and challenge the development of targeted therapies.

Applying design of experiments (DOE) to flavonoid extraction from Passiflora alata and P. edulis

The Passifloraceae family is extensively used in native Brazilian folk medicine to treat a wide variety of diseases. The problem of flavonoid extraction from Passiflora was treated by application of design of experiments (DOE), as an experiment with mixture including one categorical process variable. The components of the binary mixture were: ethanol (component A) and water (component B); the categorical process variable: extraction method (factor C) was varied at two levels: (+1) maceration and (-1) percolation. ANOVA suggested a cubic model for P. edulis extraction and a quadratic model for P. alata.These results indicate that the proportion of components A and B in the mixture is the main factor involved in significantly increasing flavonoid extraction. In regard to the extraction methods, no important differences were observed, which indicates that these two traditional extraction methods could be effectively used to extract flavonoids from both medicinal plants. The evaluation of antioxidant activity of the extract by ORAC method showed that P. edulis displays twice as much antioxidant activity as P. alata. Considering that maceration is a simple, rapid and environmentally friendly extraction method, in this study, the optimized conditions for flavonoid extraction from these Passiflora species is maceration with 75% ethanol for P. edulis and 50% ethanol for P. alata.

The star formation rate in the inner Milky Way Galaxy

The present star formation rate (SFR) in the inner Galaxy is puzzling for the chemical evolution models (CEM). No static CEM is able to reproduce the peak of the SFR in the 4 kpc ring. The main reason is probably a shortage of gas, which could be due to the dynamical effects produced by the galactic bar, not considered by these models. We developed a CEM that includes radial gas flows in order to mimic the effects of the galactic bar in the first 5 kpc of the galactic disk. In this model, the star formation (SF) is a two-step process: first, the diffuse gas forms molecular clouds. Then, stars form from cloud-cloud collisions or by the interaction between massive stars and the molecular gas. The former is called spontaneous and the latter induced SF. The mass in the different phases of each region changes by the processes associated with the stellar formation and death by: the SF due to spontaneous fragmentation of gas in the halo; formation of gas clouds in the disk from the diffuse gas; induced SF in the disk due to the interaction between massive stars and gas clouds; and finally, the restitution of the diffuse gas associated to these process of cloud and star formation. In the halo, the star formation rate for the diffuse gas follows a Schmidt law with a power n = 1.5. In the disk, the stars form in two steps: first, molecular clouds are formed from the diffuse gas also following a Schmidt law with n=1.5 and a proportionality factor. Including a specific pattern of radial gas flows, the CEM is able to reproduce with success the peak in the SFR at 4 kpc (fig. 1).

Numeric reconstruction of cytoskeleton with finite element method and topology optimization method

The importance of mechanical aspects related to cell activity and its environment is becoming more evident due to their influence in stem cell differentiation and in the development of diseases such as atherosclerosis. The mechanical tension homeostasis is related to normal tissue behavior and its lack may be related to the formation of cancer, which shows a higher mechanical tension. Due to the complexity of cellular activity, the application of simplified models may elucidate which factors are really essential and which have a marginal effect. The development of a systematic method to reconstruct the elements involved in the perception of mechanical aspects by the cell may accelerate substantially the validation of these models. This work proposes the development of a routine capable of reconstructing the topology of focal adhesions and the actomyosin portion of the cytoskeleton from the displacement field generated by the cell on a flexible substrate. Another way to think of this problem is to develop an algorithm to reconstruct the forces applied by the cell from the measurements of the substrate displacement, which would be characterized as an inverse problem. For these kind of problems, the Topology Optimization Method (TOM) is suitable to find a solution. TOM is consisted of an iterative application of an optimization method and an analysis method to obtain an optimal distribution of material in a fixed domain. One way to experimentally obtain the substrate displacement is through Traction Force Microscopy (TFM), which also provides the forces applied by the cell. Along with systematically generating the distributions of focal adhesion and actin-myosin for the validation of simplified models, the algorithm also represents a complementary and more phenomenological approach to TFM. As a first approximation, actin fibers and flexible substrate are represented through two-dimensional linear Finite Element Method. Actin contraction is modeled as an initial stress of the FEM elements. Focal adhesions connecting actin and substrate are represented by springs. The algorithm was applied to data obtained from experiments regarding cytoskeletal prestress and micropatterning, comparing the numerical results to the experimental ones

Which factors are important for crossmodal attentional effect?

Some results in the literature suggest that crossmodal attention is very sensitive to the features of the experimental protocol. The current work examined the possible contribution of the asynchrony between the onset of the cue and the target (SOA) and the kind of task performed by the observer to the manifestation of crossmodal attentional effect. In a first experiment, a target (Gabor patch), whose spatial frequency had to be discriminated, was presented 133 or 159 ms after an auditory cue, in a close location on the same side or in a distant location on the opposite side. The crossmodal attentional effect was observed only for the 159 ms SOA. In a second experiment, the SOA was again 133 ms, but the location of the target had to be discriminated, instead of its spatial frequency. A crossmodal attentional effect was observed. The results of these two experiments indicate that crossmodal attentional effect depends on the SOA and the task. It takes longer to develop when the task requires the discrimination of the spatial frequency of the target than the discrimination of its location.

Fatigue crack growth assessments in welded components including crack closure effects: Experiments and 3-D numerical modeling

This work provides a numerical and experimental investigation of fatigue crack growth behavior in steel weldments including crack closure effects and their coupled interaction with weld strength mismatch. A central objective of this study is to extend previously developed frameworks for evaluation of crack clo- sure effects on FCGR to steel weldments while, at the same time, gaining additional understanding of commonly adopted criteria for crack closure loads and their influence on fatigue life of structural welds. Very detailed non-linear finite element analyses using 3-D models of compact tension C ( T ) fracture spec- imens with center cracked, square groove welds provide the evolution of crack growth with cyclic stress intensity factor which is required for the estimation of the closure loads. Fatigue crack growth tests con- ducted on plane-sided, shallow-cracked C ( T ) specimens provide the necessary data against which crack closure effects on fatigue crack growth behavior can be assessed. Overall, the present investigation pro- vides additional support for estimation procedures of plasticity-induced crack closure loads in fatigue analyses of structural steels and their weldments

One and two degrees-of-freedom Vortex-Induced Vibration experiments with yawed cylinders

Vortex-Induced Vibration (VIV) experiments were carried out with yawed cylinders. The purpose was to investigate the validity of the Independence Principle (IP) for properly describing the flow characteristics and the dynamics of structures subjected to oblique flow. Five yaw angles in relation to the direction perpendicular to the free stream velocity were tested, namely View the MathML sourceθ=0°,10°,20°,30° and 45°. Both the upstream and downstream orientations were tested. The models were mounted on a leaf spring apparatus that allows experiments with one or two degrees of freedom. The Reynolds numbers based on the component normal to the cylinder axis fell in the interval 3×103experiments. Time histories of displacement and hydrodynamic forces were acquired. Considering only the component of the free stream which is normal to the cylinder axis, the results of amplitude and force coefficients agreed reasonably well with the non-yawed ones for yaw angles up to 20° for both one and two degrees-of-freedom experiments. This indicates the validity of the IP for this yaw angle range. For yaw angles larger than 20°, a decrease in the maximum amplitude was observed. The decrease in the oscillation amplitudes was related to a larger modulation in the phase shift between force and displacement. Differences in the results for upstream and downstream were observed and were more evident for the larger yaw angle. These differences can be associated to the asymmetric cylinder end conditions.